KalVista's Sebetralstat NDA Accepted by FDA for On-Demand Hereditary Angioedema Treatment

KalVista Pharmaceuticals, Inc. has announced that the U.S. Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) for sebetralstat. Sebetralstat is a novel, investigational oral plasma kallikrein inhibitor designed for the on-demand treatment of hereditary angioedema (HAE) attacks in patients aged 12 years and above. The FDA has set a target decision date of June 17, 2025, under the Prescription Drug User Fee Act (PDUFA). If approved, sebetralstat would become the first oral, on-demand treatment available for HAE in both adults and children aged 12 and older. The FDA has indicated that it does not plan to hold an advisory committee meeting regarding this application.

KalVista's CEO, Ben Palleiko, expressed excitement over the FDA’s acceptance of the NDA, emphasizing that this milestone could lead to a transformative therapy for the HAE community. He highlighted the significant burden carried by those living with HAE, as unpredictable and potentially life-threatening attacks can occur at any time. Palleiko noted that the data supporting their application show that sebetralstat has the potential to significantly change the way HAE is managed and treated. He also acknowledged the strong support from healthcare providers, advocates, patients, and their families, and praised the dedication of the KalVista team and the support from HAE patients and advocacy organizations.

The NDA submission was bolstered by data from the KONFIDENT phase 3 clinical trial and the ongoing KONFIDENT-S open-label extension trial. Sebetralstat demonstrated efficacy in its phase 3 trial, achieving symptom relief more rapidly than placebo for both 300 mg and 600 mg dosages. Additionally, it was well-tolerated with a safety profile similar to placebo. In the KONFIDENT-S trial, patients were able to treat attacks early, with a median time from attack onset to treatment of just 9 minutes. The trial also showed consistent safety and efficacy, with a median time to symptom relief for laryngeal attacks of 1.3 hours.

KalVista has also initiated the KONFIDENT-KID clinical trial, which aims to evaluate the safety and efficacy of sebetralstat in children aged 2-11 years. This trial began ahead of schedule in June 2024 and has already started dosing patients.

In addition to the FDA's acceptance, KalVista has announced that the European Medicines Agency (EMA) has validated the submission of the Marketing Authorization Application (MAA) for sebetralstat. KalVista plans to seek approval in the UK, Japan, and other countries later in 2024.

The KONFIDENT phase 3 trial was a large, randomized, double-blind, 3-way crossover study that included 136 HAE patients from 66 clinical sites across 20 countries. The trial evaluated the safety and efficacy of 300 mg and 600 mg doses of sebetralstat compared to placebo for on-demand HAE treatment. Participants treated eligible attacks with the study drug and could treat up to three attacks during the trial. The trial included patients with type 1 and type 2 HAE, even those on long-term prophylaxis.

The ongoing KONFIDENT-S open-label extension trial assesses the long-term safety and efficacy of sebetralstat for on-demand HAE treatment. KalVista plans to transition participants to an oral disintegrating tablet (ODT) formulation later in 2024, with the goal of filing for an additional NDA for this formulation in 2026.

The KONFIDENT-KID trial enrolls approximately 24 children aged 2 to 11 years and collects data on the safety, pharmacokinetics, and efficacy of sebetralstat over a year. If approved, sebetralstat would be the first oral on-demand therapy for this age group and the second FDA-approved on-demand therapy of any type for this population.

Sebetralstat, discovered and developed by KalVista's scientific team, is an innovative oral plasma kallikrein inhibitor for HAE treatment. It has received Fast Track and Orphan Drug Designations from the FDA, as well as Orphan Drug Designation and an approved Pediatric Investigational Plan from the EMA.

Hereditary angioedema (HAE) is a rare genetic disorder characterized by painful and debilitating tissue swelling attacks. Current on-demand treatments require intravenous or subcutaneous administration, highlighting the potential impact of an oral treatment option like sebetralstat.

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